Mechanism of thioflavin T binding to amyloid fibrils

Khurana, Rohit; Coleman, Chris L.; Ionescu-Zanetti, Cristian; Carter, Sue A.; Krishna, Vinay; Grover, Rajesh K.; Roy, Raja; Singh, Shashi

doi:10.1016/j.jsb.2005.06.006

Cited by 732 publications

(617 citation statements)

References 17 publications

Supporting

Mentioning

570

Contrasting

Unclassified

Order By: Relevance

“…Thioflavin T, which has fluorescent properties, is a dye that is generally used for observing and quantifying amyloid assembly under both in vivo and in vitro conditions in such a way that the fluorescence intensity is increased by connection to amyloid fibrils [22]. In this study, an enhancement in the ThT fluorescence following the incubation of Aβ 42 peptide was observed, implying amyloid formation in the peptide (Fig.…”

Section: Thioflavin T-binding Assaysupporting

confidence: 49%

The protective effect of crocin on the amyloid fibril formation of aβ42 peptide in vitro

Ghahghaei

Bathaie

Kheirkhah

et al. 2013

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

Abstract:Aβ is the main constituent of the amyloid plaque found in the brains of patients with Alzheimer's disease. There are two common isoforms of Aβ: the more common form, Aβ 40 , and the less common but more amyloidogenic form, Aβ 42 . Crocin is a carotenoid from the stigma of the saffron flower and it has many medicinal properties, including antioxidant effects. In this study, we examined the potential of crocin as a drug candidate against Aβ 42 amyloid formation. The thioflavin T-binding assay and electron microscopy were used to examine the effects of crocin on the extension and disruption of Aβ 42 amyloids. To further investigate the relationship between crocin and Aβ 42 structure, we analyzed peptide conformation using the ANS-binding assay and circular dichroism (CD) spectroscopy. An increase in the thioflavin T fluorescence intensity upon incubation revealed amyloid formation in Aβ 42 . It was found that crocin has the ability to prevent amyloid formation by decreasing the fluorescence intensity. Electron microscopy data also indicated that crocin decreased the amyloid fibril content of Aβ. The ANS-binding assay showed that crocin decreased the hydrophobic area in incubated Aβ 42 . CD spectroscopy results also showed that the peptide undergoes a structural change to α-helical and β-turn. Our study shows that the anti-amyloidogenic effect of crocin may be exerted not only by the inhibition of Aβ amyloid formation but also by the Unauthenticated Download Date | 5/12/18 7:38 AM CELLULAR & MOLECULAR BIOLOGY LETTERS 329 disruption of amyloid aggregates. Therefore, crocin could be essential in the search for therapies inhibiting aggregation or disrupting aggregation.

show abstract

Section: Thioflavin T-binding Assaysupporting

confidence: 49%

The protective effect of crocin on the amyloid fibril formation of aβ42 peptide in vitro

Ghahghaei

Bathaie

Kheirkhah

et al. 2013

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

show abstract

“…Fluorescence studies over a 30-day incubation period revealed an increase in the fluorescence intensity for the samples incubated with fructose invitro. ThT is used as a diagnostic dye for the amyloid fibrils due to its geometric fitness and therefore, binding to these structures [28,29]. Increase in fluorescence property of ThT upon interaction with AGE-Hb demonstrates the evolving of amyloid-like structure.…”

Section: Discussionmentioning

confidence: 99%

Platelet Aggregation Increased by Advanced Glycated Hemoglobin

M¹

2015

J Blood Disord Transfus

View full text Add to dashboard Cite

show abstract

“…For these molecules the increase in fluorescence is assumed to originate from the rigid and/or hydrophobic environment at the binding site of the aggregates [30][31][32]. Although these compounds have been studied extensively, the fluorescence mechanism and the origin of the fluorescence increase upon binding are still controversial [31,[33][34][35]. For the DPPcompounds one may assume that a rigid environment at the binding sites of the fibrillar aggregates [30] could reduce the intrinsic flexibility of the compounds and with that could slow down internal conversion processes.…”

Section: Absorption and Emission Propertiesmentioning

confidence: 99%

Anle138b and related compounds are aggregation specific fluorescence markers and reveal high affinity binding to α-synuclein aggregates

Deeg

Reiner

Schmidt

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Background: Special diphenyl-pyrazole compounds and in particular anle138b were found to reduce the progression of prion and Parkinson's disease in animal models. The therapeutic impact of these compounds was attributed to the modulation of α-synuclein and prion-protein aggregation related to these diseases. Methods: Photophysical and photochemical properties of the diphenyl-pyrazole compounds anle138b, anle186b and sery313b and their interaction with monomeric and aggregated α-synuclein were studied by fluorescence techniques. Results: The fluorescence emission of diphenyl-pyrazole is strongly increased upon incubation with α-synuclein fibrils, while no change in fluorescence emission is found when brought in contact with monomeric α-synuclein. This points to a distinct interaction between diphenyl-pyrazole and the fibrillar structure with a high binding affinity (K d = 190 ± 120 nM) for anle138b. Several α-synuclein proteins form a hydrophobic binding pocket for the diphenyl-pyrazole compound. A UV-induced dehalogenation reaction was observed for anle138b which is modulated by the hydrophobic environment of the fibrils. Conclusion: Fluorescence of the investigated diphenyl-pyrazole compounds strongly increases upon binding to fibrillar α-synuclein structures. Binding at high affinity occurs to hydrophobic pockets in the fibrils. General significance: The observed particular fluorescence properties of the diphenyl-pyrazole molecules open new possibilities for the investigation of the mode of action of these compounds in neurodegenerative diseases. The high binding affinity to aggregates and the strong increase in fluorescence upon binding make the compounds promising fluorescence markers for the analysis of aggregation-dependent epitopes.

show abstract

Mechanism of thioflavin T binding to amyloid fibrils

Cited by 732 publications

References 17 publications

The protective effect of crocin on the amyloid fibril formation of aβ42 peptide in vitro

The protective effect of crocin on the amyloid fibril formation of aβ42 peptide in vitro

Platelet Aggregation Increased by Advanced Glycated Hemoglobin

Anle138b and related compounds are aggregation specific fluorescence markers and reveal high affinity binding to α-synuclein aggregates

Contact Info

Product

Resources

About